Objective: Risperidone is one of the most commonly prescribed antipsychotics worldwide. Its main metabolite, 9-hydroxyrisperidone (9-OH-RIS), is excreted renally. The present study examined the relationship of kidney function and serum risperidone concentrations in a large sample of risperidone-treated patients.
Methods: Serum concentrations of risperidone and its active metabolite 9-OH-RIS, as well as creatinine concentrations, from which glomerular filtration rates (GFRs) were estimated, were determined in 175 risperidone-medicated patients (75 female, 100 male). Data were collected between July 2013 and December 2016. Patients were clustered in 4 groups according to their estimated GFR (eGFR) (30-60; > 60-90; > 90-120; and > 120 mL/min/1.73 m²), and serum concentrations of risperidone and 9-OH-RIS and their sum (active moiety [AM]) were compared groupwise. Additionally, serum concentrations were correlated with kidney function.
Results: Dose-corrected AM and dose-corrected 9-OH-RIS concentrations were significantly higher in patients with an eGFR of 30-60 mL/min/1.73 m² than in patients with an eGFR > 90-120 mL/min/1.73 m² (P < .001 for dose-corrected AM and P = .001 for dose-corrected 9-OH-RIS) or > 120 mL/min/1.73 m² (P = .036 and .021, respectively). Dose-corrected AM levels were more than doubled in the 30-60 mL/min/1.73 m² group compared to the > 90-120 mL/min/1.73 m² group (mean ± SD = 22.2 ± 14.0 [ng/mL]/[mg/d] vs 10.1 ± 7.7 [ng/mL]/[mg/d]). In the total group, eGFR and dose-corrected 9-OH-RIS and dose-corrected AM were weakly but statistically significantly correlated (Spearman rank correlation coefficient [Rs] = -0.2, P = .004, and Rs = -0.17, P = .01, respectively).
Conclusions: Kidney function is an important determinant of risperidone clearance. These data suggest reducing the risperidone dose by 50% in patients with a GFR below 60 mL/min.
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